Transfer RNA Modification

Yuri Motorin, Laboratoire MAEM, Vandoeuvre‐les‐Nancy, France
Henri Grosjean, Laboratoire d'Enzymologie et Biologie Structurales, Gif‐sur‐Yvette, France

Published online: September 2005

DOI: 10.1038/npg.els.0003866

Full Article on Wiley Online Library

Naturally occurring transfer ribonucleic acid (tRNA) always contains numerous chemically altered nucleosides formed by enzymatic modification of the primary RNA transcript during the complex tRNA maturation process. These modifications favour correct folding and stabilize the tRNA architecture, protect RNAs against nucleolytic degradation and improve its performance in the different interactions in which tRNA is involved, namely in aminoacylation by cognate aminoacyl-tRNA synthetases, interactions with initiation and elongation factors as well as in decoding of messenger RNA on the ribosome. In eukaryotic cells, RNA modification may also help in tRNA transport across internal membranes.

Keywords: translation; protein synthesis; modified nucleotides; RNA maturation

References
	McCloskey J and Crain P (1999) The RNA modification database: 1999 update–. Nucleic Acids Research 27: 196–197 [http://medlib.med.utah.edu/RNAmods/].
	Sprinzl S, Hartmann T, Weber J, Blank J and Zeiler R (1999) Compilation of tRNA sequences and sequences of tRNA genes. Nucleic Acids Research 17(Suppl.): r1–r67 [http://www.uni-bayreuth.de/departments/biochemie/trna/].
Further Reading
	Agris P (1996) The importance of being modified: roles of modified nucleosides and Mg²⁺ in RNA structure and function. Progress in Nucleic Acid Research and Molecular Biology 53: 79–129.
	Anantharaman V, Koonin EV and Aravind L (2002) Comparative genomics and evolution of proteins involved in RNA metabolism (survey and summary). Nucleic Acids Research 30: 1427–1464.
	Ansmant I and Motorin Y (2001) Identification of tRNA modification enzymes using sequence homology. Molecular Biology 345: 206–223.
	Björk GR (1995) Genetic dissection of synthesis and function of modified nucleosides in bacterial transfer RNA. Progress in Nucleic Acid Research and Molecular Biology 50: 263–338.
	Ferré-D'Amaré AR (2003) RNA-modifying enzymes. Current Opinion in Structural Biology 13: 49–55.
	book Grosjean H (ed.) (2005) Current Topics in Genetics, Vol. 12: Fine-tuning of RNA Functions by Modification and Editing. Berlin: Springer-Verlag.
	book Grosjean H and Benne R (1998) Modification and Editing of RNA. Washington, DC: ASM Press (29 chapters and 6 appendices).
	book Grosjean H, Keith G and Droogmans L (2004) "Detection and quantification of modified nucleotides in RNA using thin-layer chromatography". In: JM Gott (ed) RNA Interference, Editing and Modification – Methods in Molecular Biology. Humana Press, NJ (in press).
	Hopper AK and Phizicky EM (2003) tRNA transfers to limelight. Genes and Development 17: 162–180.
	Omer AD, Ziesche S, Decatur WA, Fournier MJ and Dennis PD (2003) RNA-modifying machines in archaea. Molecular Microbiology 48: 617–629.
	book Yokoyama S and Nishimura S (1995) "Modified nucleosides and codon recognition". In: Söll D and RajBhandary U (eds) tRNA: Structure, Biosynthesis and Function, pp. 207–224. Washington, DC: ASM Press.

Article Title:	Transfer RNA Modification
* Name:
* E-mail:
* Note:

	Figure 1. Types of chemical alterations and their location within the purine and pyrimidine derivatives in all kinds of RNAs (tRNA, rRNA, mRNA, snRNA, etc.) from various organisms. The groups that differentiate from the canonical A, G, C or U are in red and magenta. In naturally occurring tRNAs, various combinations of these different modifications exist, thus extending the total number of the modified nucleosides present in RNAs to up to 100. Except for 7-deazaguanosine and queuosine derivatives, the purine and pyrimidine ring (in black) are those initially encoded in RNA during transcription.The sign ‘+’ for m¹A, m⁷G, k²C and gQ/G⁺ indicates a positive charge under the physiological pH of the cell. For more details about the chemistry and occurrence of modified nucleosides in RNA, see Sprinzl et al. (1999) or McCloskey and Crain (1999).
	Figure 2. Modification patterns of tRNA from organisms of the three phylogenetic domains: Eubacteria (E. coli, 45 sequences), Archaea (H. volcanii, 41 sequences) and Eukaryota (lower eukaryote S. cerevisiae, 34 sequences and higher eukaryotes rat, bovine, rabbit and human, 44 sequences). For eukaryotic tRNA, only cytoplasmic species have been taken into account. Numbers indicate conventional tRNA positions. The most frequently modified sites are circled in bold. Abbreviations of modified nucleosides are those of Figure 1; see also Sprinzl et al. (1999) or McCloskey and Crain (1999).
	Figure 3. Phylogenetic distribution of modified nucleosides in tRNA originating from the three domains of life. Abbreviations of modified nucleosides are as in Figure 1. Modified nucleosides with yellow background correspond to those that are exclusively present in eukaryotic mitochondrial tRNAs. Data presented in this figure may be in contradiction with other sources due to: (i) limited information available on the RNA sequence of many Archaea tRNAs, (ii) discrepancies between direct tRNA sequencing data and global nucleoside composition analysis by HPLC-MS and (iii) errors, misinterpretation or misidentification of modified residues in tRNA molecules. Updated from Motorin Y and Grosjean H (1998) Chemical structures and classification of posttranscriptionally modified nucleosides in RNA. In: Grosjean H and Benne R (eds) The Modification and Editing of RNA, pp. 543–549. ASM Press, New York, with permission from The American Society for Microbiology.

Transfer RNA Modification

Related Sub-Topics: